puc-header

Integration of Genomic and Transcriptomic Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases

44 Pages Posted: 6 Jun 2018 Sneak Peek Status: Review Complete

See all articles by Ashton A. Connor

Ashton A. Connor

University of Toronto - Department of Surgery; Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Robert E. Denroche

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Gun Ho Jang

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Mathieu Lemire

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Amy Zhang

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Michelle Chan-Seng-Yue

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Gavin Wilson

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Daniele Merico

Deep Genomics Inc.

Ilinca Lungu

Ontario Institute for Cancer Research - Diagnostic Development

John M. S. Bartlett

Ontario Institute for Cancer Research - Diagnostic Development

Dianne Chadwick

University Health Network - UHN Biobank

Sheng-Ben Liang

University Health Network - UHN Biobank

Jenna Eagles

Ontario Institute for Cancer Research - Department of Genomics

Faridah Mbabaali

Ontario Institute for Cancer Research - Department of Genomics

Jessica K. Miller

Ontario Institute for Cancer Research - Department of Genomics

Paul Krzyzanowski

Ontario Institute for Cancer Research - Department of Genomics

Heather Armstrong

Ontario Institute for Cancer Research - Department of Genome Sequence Informatics

Xuemei Luo

Ontario Institute for Cancer Research - Department of Genome Sequence Informatics

Lars G. T. Jorgensen

Ontario Institute for Cancer Research - Department of Genome Sequence Informatics

Joan M. Romero

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Prashant Bavi

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Sandra E. Fischer

University of Toronto - Department of Laboratory Medicine and Pathobiology

Stefano Serra

University Health Network - Department of Pathology

Sara Hafezi Bakhtiari

University Health Network - Department of Pathology

Derin Caglar

McGill University - Department of Pathology

Michael H. A. Roehrl

University Health Network - UHN Biobank

Sean Cleary

Mayo Clinic

Michael A. Hollingsworth

University of Nebraska at Omaha - Medical Center

Gloria Petersen

Mayo Clinic - College of Medicine and Science

Sarah Thayer

Harvard University - Massachusetts General Hospital

Calvin H. L. Law

Sunnybrook Health Sciences Centre - Department of Surgery

Sulaiman Nanji

Kingston General Hospital - Department of Surgery

Talia Golan

Tel Aviv University - Sackler Faculty of Medicine

Alyssa L. Smith

McGill University - Research Institute

Ayelet Borgida

University of Toronto - Lunenfeld-Tanenbaum Research Institute

Anna Dodd

University Health Network - Wallace McCain Centre for Pancreatic Cancer

David Hedley

University Health Network - Department of Medical Oncology

Bradly G. Wouters

University Health Network - Princess Margaret Cancer Centre

Grainne M. O’Kane

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Julie M. Wilson

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

George Zogopoulos

McGill University - Research Institute

Faiyaz Notta

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Jennifer J. Knox

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

Steven Gallinger

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

More...

Abstract

We integrated clinical, genomic and transcriptomic data from 217 primaries and 101 metastases from 289 patients to characterize progression of pancreatic ductal adenocarcinoma. Driver genes alterations, mutational and expression-based signatures were mostly preserved, and discordances implied Halstedian tumour spread. Cell cycle progression increased with sequential inactivation of tumour suppressors, yet remained higher in metastases, perhaps driven by cell cycle regulatory gene mutations. Half of the cases were hypoxic by expression markers, overlapping with molecular subtypes. Inter-tumoural heterogeneity showed conserved truncations, inversions and translocations and therefore likely driver events. Multiple synchronous and metachronous PDAC arising in the same patients were actually intra-parenchymal metastases, and not independent primary tumours. Established clinical co-variates dominated survival analyses, though cell cycle progression, hypoxia and inter-tumoural heterogeneity may inform clinical practice.

Suggested Citation

Connor, Ashton A. and Denroche, Robert E. and Jang, Gun Ho and Lemire, Mathieu and Zhang, Amy and Chan-Seng-Yue, Michelle and Wilson, Gavin and Merico, Daniele and Lungu, Ilinca and Bartlett, John M. S. and Chadwick, Dianne and Liang, Sheng-Ben and Eagles, Jenna and Mbabaali, Faridah and Miller, Jessica K. and Krzyzanowski, Paul and Armstrong, Heather and Luo, Xuemei and Jorgensen, Lars G. T. and Romero, Joan M. and Bavi, Prashant and Fischer, Sandra E. and Serra, Stefano and Bakhtiari, Sara Hafezi and Caglar, Derin and Roehrl, Michael H. A. and Cleary, Sean and Hollingsworth, Michael A. and Petersen, Gloria and Thayer, Sarah and Law, Calvin H. L. and Nanji, Sulaiman and Golan, Talia and Smith, Alyssa L. and Borgida, Ayelet and Dodd, Anna and Hedley, David and Wouters, Bradly G. and O’Kane, Grainne M. and Wilson, Julie M. and Zogopoulos, George and Notta, Faiyaz and Knox, Jennifer J. and Gallinger, Steven, Integration of Genomic and Transcriptomic Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases (2018). Available at SSRN: https://ssrn.com/abstract=3188387 or http://dx.doi.org/10.2139/ssrn.3188387
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Ashton A. Connor

University of Toronto - Department of Surgery

Stewart Building
149 College Street, 5th Floor
Toronto, Ontario M5T 1P5
Canada

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Robert E. Denroche

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Gun Ho Jang

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Mathieu Lemire

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Amy Zhang

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Michelle Chan-Seng-Yue

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Gavin Wilson

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Daniele Merico

Deep Genomics Inc.

661 University Ave #480
Toronto, ON M5G 1M1
Canada

Ilinca Lungu

Ontario Institute for Cancer Research - Diagnostic Development

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

John M. S. Bartlett

Ontario Institute for Cancer Research - Diagnostic Development

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Dianne Chadwick

University Health Network - UHN Biobank

101 College Street
Toronto, ON M5G 1L7
Canada

Sheng-Ben Liang

University Health Network - UHN Biobank

101 College Street
Toronto, ON M5G 1L7
Canada

Jenna Eagles

Ontario Institute for Cancer Research - Department of Genomics

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Faridah Mbabaali

Ontario Institute for Cancer Research - Department of Genomics

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Jessica K. Miller

Ontario Institute for Cancer Research - Department of Genomics

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Paul Krzyzanowski

Ontario Institute for Cancer Research - Department of Genomics

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Heather Armstrong

Ontario Institute for Cancer Research - Department of Genome Sequence Informatics

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Xuemei Luo

Ontario Institute for Cancer Research - Department of Genome Sequence Informatics

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Lars G. T. Jorgensen

Ontario Institute for Cancer Research - Department of Genome Sequence Informatics

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Joan M. Romero

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Prashant Bavi

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Sandra E. Fischer

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

Stefano Serra

University Health Network - Department of Pathology

101 College Street
Toronto, ON M5G 1L7
Canada

Sara Hafezi Bakhtiari

University Health Network - Department of Pathology

101 College Street
Toronto, ON M5G 1L7 ON M5G 1L7
Canada

Derin Caglar

McGill University - Department of Pathology

1001 Decarie Blvd
Montreal, QC H4A 3J1
Canada

Michael H. A. Roehrl

University Health Network - UHN Biobank

101 College Street
Toronto, ON M5G 1L7
Canada

Sean Cleary

Mayo Clinic

200 First Street SW
Rochester, MN (507) 284-2511 55905
United States

Michael A. Hollingsworth

University of Nebraska at Omaha - Medical Center

984350 Nebraska Medical Center
Omaha, NE 68198-4350
United States

Gloria Petersen

Mayo Clinic - College of Medicine and Science ( email )

200 First Street S.W
Rochester, MN 55905
United States

Sarah Thayer

Harvard University - Massachusetts General Hospital

55 Fruit Street Boston
Boston, MA 02114
United States

Calvin H. L. Law

Sunnybrook Health Sciences Centre - Department of Surgery

2075 Bayview Ave
Toronto, OR
Canada

Sulaiman Nanji

Kingston General Hospital - Department of Surgery

76 Stuart St.
Kingston, Ontario
Canada

Talia Golan

Tel Aviv University - Sackler Faculty of Medicine

Tel Aviv University
Ramat Aviv, 69978
Israel

Alyssa L. Smith

McGill University - Research Institute

1001 Decarie Blvd
Montreal, QC H4A 3J1
Canada

Ayelet Borgida

University of Toronto - Lunenfeld-Tanenbaum Research Institute

600 University Ave
Toronto, Ontario
Canada

Anna Dodd

University Health Network - Wallace McCain Centre for Pancreatic Cancer

610 University Avenue
Toronto, ON M5G 2M9
Canada

David Hedley

University Health Network - Department of Medical Oncology

610 University Avenue
Toronto, ON M5G 2M9
Canada

Bradly G. Wouters

University Health Network - Princess Margaret Cancer Centre

610 University Avenue
Toronto, ON M5G 2M9
Canada

Grainne M. O’Kane

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Julie M. Wilson

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative ( email )

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

George Zogopoulos

McGill University - Research Institute

1001 Decarie Blvd
Montreal, QC H4A 3J1
Canada

Faiyaz Notta

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Jennifer J. Knox

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Steven Gallinger (Contact Author)

Ontario Institute for Cancer Research - PanCuRx Translational Research Initiative ( email )

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
555
Downloads
37